We have recently found that, at a young age, transient receptor potential vanilloid-1 (Trpv1) knockout (/) mice have a higher locomotor activity than their wild-type littermates (+/+). We have also found that, with age, Trpv1−/− mice become substantially heavier than Trpv1+/+ controls, thus forming a paradoxical association between locomotor hyperactivity and overweight. The present study solves this contradiction. By using two experimental paradigms, we show that aged Trpv1−/− mice have not an increased, but a decreased, locomotor activity, as compared to age-matched Trpv1+/+ controls. We also confirm that aged Trpv1−/− mice are overweight. We conclude that TRPV1 channels are involved in the regulation of both general locomotor activity and body mass in an age-dependent manner.